Triarhou L C, Norton J, Ghetti B
Department of Pathology (Neuropathology), Indiana University School of Medicine, Indianapolis 46223.
J Neurocytol. 1988 Apr;17(2):221-32. doi: 10.1007/BF01674209.
Striatal dopamine deficiency in weaver mutant mice is associated with loss of mesencephalic dopamine neurons. The maximum dopamine concentration in the striatum of weaver mutants is found on postnatal day 20, when it represents 50% of the control value. By day 180, it declines to 25% of the control value. Correspondingly, the number of nigral dopamine neurons is 58% of the normal number on day 20 and becomes 31% of the normal value by day 90. The aim of the present study was to examine whether dopamine axon terminals in the weaver striatum establish synaptic connections with postsynaptic neurons at the time when striatal dopamine concentration is at its peak value (i.e. on postnatal day 20), and if so, to compare the profile of synaptic connectivity of dopamine axon terminals found in the striatum of normal mice with that of heterozygous and homozygous weaver mutants. To that end, 20-day-old weaver homozygotes, along with age-matched weaver heterozygotes and wild-type mice were studied by electron microscopy after immunocytochemical labelling for tyrosine hydroxylase. A single micrograph of each of 1543 dopamine axon terminals was examined in total in the three genotypes; quantitative analyses of the relations of tyrosine hydroxylase immunoreactive nerve terminals were carried out in the dorsolateral striatum, which receives the dopamine projection from the substantia nigra proper. In all three genotypes, junctional contacts formed by tyrosine hydroxylase immunoreactive nerve terminals in the striatum were predominantly of the symmetrical type. In wild-type and heterozygous mice, the majority of contacts (92% and 91% respectively) were formed with dendrites and spines. In weaver mutant mice, the majority of contacts (87%) were also with dendrites and spines, but the proportion of axosomatic contacts was double that found in normal animals. The proportions of contacts that displayed junctional membrane specializations in single sections were 27% in wild-type mice, 29% in weaver heterozygotes, and 17% in homozygous weaver mutants. Taking into consideration that the plane of the section might not always have included the synaptic specialization, a stereological formula was applied. It was estimated that 85-89% of the contacts may be truly junctional in the striatum of normal and heterozygous mice, whereas only 53% may be junctional in the striatum of weaver homozygotes. The reduced incidence of junctional synapses in weaver homozygotes may suggest either inadequate synaptogenesis, or an early loss of synapses after their formation, or both.(ABSTRACT TRUNCATED AT 400 WORDS)
织工突变小鼠纹状体多巴胺缺乏与中脑多巴胺神经元的丧失有关。在出生后第20天，发现织工突变体纹状体中的多巴胺浓度最高，此时它相当于对照值的50%。到第180天，它下降到对照值的25%。相应地，黑质多巴胺神经元的数量在第20天是正常数量的58%，到第90天变为正常值的31%。本研究的目的是检查在纹状体多巴胺浓度达到峰值时（即出生后第20天），织工纹状体中的多巴胺轴突终末是否与突触后神经元建立突触连接，如果是，则比较正常小鼠纹状体中发现的多巴胺轴突终末的突触连接情况与杂合子和纯合子织工突变体的情况。为此，在对酪氨酸羟化酶进行免疫细胞化学标记后，通过电子显微镜对20日龄的织工纯合子以及年龄匹配的织工杂合子和野生型小鼠进行了研究。总共检查了三种基因型中1543个多巴胺轴突终末的每一个的单张显微照片；在接受来自黑质本身的多巴胺投射的背外侧纹状体中，对酪氨酸羟化酶免疫反应性神经终末的关系进行了定量分析。在所有三种基因型中，纹状体中由酪氨酸羟化酶免疫反应性神经终末形成的连接接触主要是对称型。在野生型和杂合子小鼠中，大多数接触（分别为92%和91%）是与树突和棘形成的。在织工突变小鼠中，大多数接触（87%）也是与树突和棘形成的，但轴体接触的比例是正常动物中的两倍。在单张切片中显示有连接膜特化的接触比例在野生型小鼠中为27%，在织工杂合子中为29%，在织工纯合子中为17%。考虑到切片平面可能并不总是包含突触特化，应用了一种体视学公式。据估计，在正常和杂合子小鼠的纹状体中，85 - 89%的接触可能是真正的连接性接触，而在织工纯合子的纹状体中只有53%可能是连接性接触。织工纯合子中连接性突触发生率的降低可能表明突触形成不足，或者突触形成后早期丧失，或者两者皆有。（摘要截断于400字）
